Norwegian Birth Cohort Research Articles

Attention-deficit hyperactivity disorder symptoms and bullying victimization from childhood to adolescence - A within-person cross-lagged approach.

Attention-deficit hyperactivity disorder (ADHD) and subclinical symptoms of hyperactivity-impulsivity and inattentiveness coincide with an increased risk of peer victimization. What remains unclear are the developmental dynamics of these associations. In a sample drawn from two Norwegian birth cohorts (n = 872; 49.94 % girls), assessed biennially from age 6 to age 14, reciprocal relations between ADHD symptoms and victimization were examined while controlling for symptoms of anxiety and depression. ADHD symptoms were assessed through clinical interviews with parents, whereas victimization was reported by teachers using questionnaires. Random-intercept cross-lagged panel modeling revealed a consistent reciprocal within-person effect of increased ADHD symptoms on victimization, and vice versa. Analyses of subdimensions of ADHD projected a consistent cross-lagged bidirectional relationship between victimization and inattentiveness symptoms only, whereas no such reciprocity was found for hyperactivity-impulsivity symptoms. Results did not differ by gender. Findings suggest that the social context may constitute a vulnerability factor in the etiology of the inattentive subtype of ADHD, and at the same time, that inattentiveness symptoms pose a risk for becoming victimized.

Spatial inequality in higher education: a growing urban–rural educational gap?

Abstract Scholars have consistently found that inequalities in educational attainment are most pronounced along social origin and gender dimensions, but urban–rural inequalities have also been evident in recent years. A spatial gradient in educational attainment reflects how rural students are consistently less likely to gain higher education (HE) credentials than their urban peers. By drawing on full-population administrative data on the Norwegian birth cohorts from 1965 to 1989 (n = 1,419,406), followed from age 16 to 30, this article analyses how urban–rural differences in HE have changed over the last 25 years, and furthermore, whether urban–rural disparities have developed in distinct ways based on students’ social origin and gender. The results show that urban–rural disparities in higher educational attainment have become more pronounced for recent birth cohorts and particularly evident for post-1980 cohorts. This applies to students originating from both privileged and less privileged families. However, urban–rural inequalities are more evident for men than women, which over time has led gender differences to become considerably greater in rural areas. The results demonstrate that spatial inequality requires further attention in educational and stratification research, as the outcomes suggest that the urban–rural educational gap is not necessarily consistent over time.

Trends in ages at death of Norwegian centenarians: the 1870-1904 birth cohorts.

With rapidly rising life expectancy and ageing populations, interest has grown in the survival patterns and ages at death at the highest ages. In Scandinavia, the accumulation of very old population segments coupled with long-established, high-quality population registers permit meaningful analysis. This study is based on individual level data from extinct Norwegian birth cohorts using data obtained from the Norwegian Civil Register System. We assess trends in the ages at death of centenarians in Norway for cohorts born between 1870 and 1904 for evidence of any secular increase using quantile regression. We observed that there is no upward trend in centenarian lifespans, in line with recent observations in Sweden, but contrary to the upward trend at the very highest percentiles as observed in Denmark. The available evidence suggests that the stagnation in centenarian lifespans may be partly due to the failure to find ways of dealing with neurodegenerative diseases.

Perinatal exposure to potential endocrine disrupting chemicals and autism spectrum disorder: From Norwegian birth cohort to zebrafish studies

BackgroundThe etiology of autism spectrum disorder (ASD) is multifactorial, involving genetic and environmental contributors such as endocrine-disrupting chemicals (EDCs). ObjectiveTo evaluate the association between perinatal exposure to 27 potential EDCs and ASD among Norwegian children, and to further examine the neurodevelopmental toxicity of associated chemicals using zebrafish embryos and larvae. Method1,199 mothers enrolled in the prospective birth-cohort (HUMIS, 2002–2009) study. Breastmilk levels of 27 chemicals were measured: polychlorinated biphenyls, organochlorine pesticides, polybrominated diphenyl ethers, and perfluoroalkyl substances as a proxy for perinatal exposure. We employed multivariable logistic regression to determine association, utilized elastic net logistic regression as variable selection method, and conducted an in vivo study with zebrafish larvae to confirm the neurodevelopmental effect. ResultsA total of 20 children had specialist confirmed diagnosis of autism among 1,199 mother–child pairs in this study. β-Hexachlorocyclohexane (β-HCH) was the only chemical associated with ASD, after adjusting for 26 other chemicals. Mothers with the highest levels of β-HCH in their milk had a significant increased risk of having a child with ASD (OR = 1.82, 95 % CI: 1.20, 2.77 for an interquartile range increase in ln-transformed β-HCH concentration). The median concentration of β-HCH in breast milk was 4.37 ng/g lipid (interquartile range: 2.92–6.47), and the estimated daily intake (EDI) for Norwegian children through breastfeeding was 0.03 µg/kg of body weight. The neurodevelopmental and social behavioral effects of β-HCH were established in zebrafish embryos and larvae across various concentrations, with further analysis suggesting that perturbation of dopaminergic neuron development may underlie the neurotoxicity associated with β-HCH. ConclusionsPrenatal exposure to β-HCH was associated with an increased risk of specialist-confirmed diagnoses of ASD among Norwegian children, and the EDI surpasses the established threshold. Zebrafish experiments confirm β-HCH neurotoxicity, suggesting dopaminergic neuron disruption as a potential underlying mechanism.

Cohort profile update: the Norwegian STORK Groruddalen (STORK G) pregnancy and birth cohort—the role of ethnicity and causal pathways for obesity, type 2 diabetes, cardiovascular disease and other health issues

PurposeThe STORK Groruddalen cohort was set up in 2008 to explore ethnic differences in: (1) maternal health, primarily gestational diabetes (GDM) and related health issues during pregnancy and post partum,...

Relative Age Within School Grade, Including Delayed and Accelerated School Start: Associations With Midlife Psychiatric Disorders, Suicide, and Alcohol- and Drug-Related Mortality.

Within a school grade, children who are young for grade are at increased risk of psychiatric diagnoses, but the long-term implications remain understudied, and associations with students who delay or accelerate entry underexplored. We used Norwegian birth cohort records (birth years: 1967-1976, n= 626,928) linked to records in midlife. On-time school entry was socially patterned; among those born in December, 23.0% of children in the lowest socioeconomic position (SEP) delayed school entry, compared with 12.2% among the highest SEP. Among those who started school on time, there was no evidence for long-term associations between birth month and psychiatric/behavioral disorders or mortality. Controlling for SEP and other confounders, delayed school entry was associated with increased risk of psychiatric disorders and mortality. Children with delayed school entry were 1.31 times more likely to die by suicide (95% confidence interval: 1.07, 1.61) by midlife, and 1.96 times more likely to die from drug-related death (95% confidence interval: 1.59, 2.40) by midlife than those born late in the year who started school on time. Associations with delayed school entry are likely due to selection, and results thus underscore that long-term health risks can be tracked early in life, including through school entry timing, and are highly socially patterned.

Predictors of Human Milk Fatty Acids and Associations with Infant Growth in a Norwegian Birth Cohort.

Triglyceride-bound fatty acids constitute the majority of lipids in human milk and may affect infant growth. We describe the composition of fatty acids in human milk, identify predictors, and investigate associations between fatty acids and infant growth using data from the Norwegian Human Milk Study birth cohort. In a subset of participants (n = 789, 30% of cohort), oversampled for overweight and obesity, we analyzed milk concentrations of detectable fatty acids. We modelled percent composition of fatty acids in relation to maternal body mass index, pregnancy weight gain, parity, smoking, delivery mode, gestational age, fish intake, and cod liver oil intake. We assessed the relation between fatty acids and infant growth from 0 to 6 months. Of the factors tested, excess pregnancy weight gain was positively associated with monounsaturated fatty acids and inversely associated with stearic acid. Multiparity was negatively associated with monounsaturated fatty acids and n-3 fatty acids while positively associated with stearic acid. Gestational age was inversely associated with myristic acid. Medium-chain saturated fatty acids were inversely associated with infant growth, and mono-unsaturated fatty acids, particularly oleic acid, were associated with an increased odds of rapid growth. Notably, excessive maternal weight gain was associated with cis-vaccenic acid, which was further associated with a threefold increased risk of rapid infant growth (OR = 2.9, 95% CI 1.2–6.6), suggesting that monounsaturated fatty acids in milk may play a role in the intergenerational transmission of obesity.

Relations between physical activity, sedentary time, and body fat from childhood to adolescence: Do they differ by sex?

Efforts to reveal the direction of influence between physical activity (PA), sedentary time (ST) and body fat in youth have produced inconsistent results, possibly due to a lack of adjustment for confounders and other factors. Sex-specific associations have rarely been studied. A sample from two Norwegian birth cohorts (n = 809) were followed biennially over five waves from the age of 6-14 years. Physical activity and ST were recorded by accelerometers, and body fat was assessed by bioelectrical impedance measurements. By applying a dynamic panel model (DPM) that adjusts for all time-invariant confounding factors, it was found that among boys, increased fat mass index (FMI) at ages 8, 10 and 12 years predicted decreased PA two years later (8-10 years: B = -0.67, (95% CI: -1.1, -0.24); 10-12 years: B = -0.33, (95% CI: -0.61, -0.05); 12-14 years: B = -0.29, (95% CI: -0.52, -0.06)). Regarding the opposite direction of influence, more PA at age 12 forecasted reduced FMI at age 14 (B = -0.16, (95% CI: -0.24, -0.07)), whereas increased FMI predicted increased ST across all time points in boys only (6-8 years: B = 0.23, (95% CI:0.02.43); 8-10 years: B = 0.23, (95% CI:.08.39); 10-12 years: B = 0.13, (95% CI:.03.23); 12-14 years: B = 0.17, (95% CI:.07, 26)). The revealed relationships were significantly stronger in boys compared to the (absent) relations in girls. Sensitivity analyses examining moderate to vigorous PA (MVPA) rather than total PA were in accordance with the main findings. In boys, increased FMI predicted reduced PA and increased ST two years later from childhood to adolescence. The opposite direction of influence was evident from only ages 12-14. There were no prospective relationships between FMI and PA or ST among girls.

Identifying a Single Optimal Integrated Cervical Cancer Prevention Policy in Norway: A Cost-Effectiveness Analysis.

Interventions targeting the same disease but at different points along the disease continuum (e.g., screening and vaccination to prevent cervical cancer [CC]) are often evaluated in isolation, which can affect cost-effectiveness profiles and policy conclusions. We evaluated nonavalent human papillomavirus (HPV) vaccine (9vHPV) compared with bivalent HPV vaccine (2vHPV) alongside deintensified screening intervals for a vaccinated birth cohort to inform a single optimal integrated CC prevention policy. Using a multimodeling approach, we evaluated the health and economic impacts of alternative CC screening strategies for a Norwegian birth cohort eligible for HPV vaccination in 2021 assuming they received 1) 2vHPV or 2) 9vHPV. We conducted 1) a restricted analysis that evaluated the optimal HPV vaccine under current screening guidelines; and 2) a comprehensive analysis including alternative screening and vaccination strategy combinations. We calculated incremental cost-effectiveness ratios (ICERs) and evaluated them according to different cost-effectiveness thresholds. Assuming a cost-effectiveness threshold of $40,000 per quality-adjusted life year (QALY) gained, we found that, while holding screening intensity fixed, switching the routine vaccination program in Norway from 2vHPV to 9vHPV would not be considered cost-effective (ICER of $132,700 per QALY gained). However, when allowing for varying intensities of CC screening, we found that switching to 9vHPV would be cost-effective compared with 2vHPV under an alternative threshold of $55,000 per QALY gained, if coupled with reductions in the number of lifetime screens. Our analysis highlights the importance of evaluating the full potential policy landscape for country-level decision makers considering policy adoption, including nonindependent primary and secondary prevention efforts, to draw appropriate conclusions and avoid sub-optimal outcomes. Without evaluating the full potential policy landscape, including primary and secondary prevention efforts, country-level decision makers may not be able to draw appropriate policy conclusions, resulting in suboptimal outcomes.An applied example from cervical cancer prevention in Norway compared a restricted analysis of current screening guidelines to a comprehensive analysis including alternative screening and vaccination strategy combinations.We found that a switch from bivalent to nonavalent human papillomavirus vaccine would be considered cost-effective in Norway if coupled with reductions in the number of lifetime screens compared with the current screening strategy.A comprehensive analysis that considers how different types of interventions along the disease continuum affect each other will be critical for decision makers interpreting cost-effectiveness analysis results.

Parental income gradients in adult health: a national cohort study

BackgroundDisparities in health by adult income are well documented, but we know less about the childhood origins of health inequalities, and it remains unclear how the shape of the gradient varies across health conditions. This study examined the association between parental income in childhood and several measures of morbidity in adulthood.MethodsWe used administrative data on seven complete Norwegian birth cohorts born in 1967–1973 (N = 429,886) to estimate the association between parental income from birth to age 18, obtained from tax records available from 1967, linked with administrative registries on health. Health measures, observed between ages 39 and 43, were taken from registry data on consultations at primary health care services based on diagnostic codes from the International Classification of Primary Care (ICPC-2) and hospitalizations and outpatient specialist consultations registered in the National Patient Registry (ICD-10).ResultsLow parental income during childhood was associated with a higher risk of being diagnosed with several chronic and pain-related disorders, as well as hospitalization, but not overall primary health care use. Absolute differences were largest for disorders related to musculoskeletal pain, injuries, and depression (7–9 percentage point difference). There were also differences for chronic disorders such as hypertension (8%, CI 7.9–8.5 versus 4%, CI 4.1–4.7) and diabetes (3.2%, CI 3.0–3.4 versus 1.4%, CI 1.2–1.6). There was no difference in consultations related to respiratory disorders (20.9%, CI 20.4–21.5 versus 19.7%, CI 19.2–20.3). Childhood characteristics (parental education, low birth weight, and parental marital status) and own adult characteristics (education and income) explained a large share of the association.ConclusionsChildren growing up at the bottom of the parental income distribution, compared to children in the top of the income distribution, had a two- to threefold increase in somatic and psychological disorders measured in adulthood. This shows that health inequalities by socioeconomic family background persist in a Scandinavian welfare-state context with universal access to health care.

Modeling Obesity in Norway (The MOON Study): A Decision-Analytic Approach-Prevalence, Costs, and Years of Life Lost.

BackgroundLimited knowledge exists on the expected long-term effects and cost-effectiveness of initiatives aiming to reduce the burden of obesity.AimTo develop a Norwegian obesity-focused disease-simulation model: the MOON model.Material and MethodsWe developed a Markov model and simulated a Norwegian birth cohort’s movement between the health states “normal weight,”“overweight,”“obese 1,”“obese 2,” and “dead” using a lifetime perspective. Model input was estimated using longitudinal data from health surveys and real-world data (RWD) from local and national registers (N = 99,348). The model is deterministic and probabilistic and stratified by gender. Model validity was assessed by estimating the cohort’s expected prevalence, health care costs, and mortality related to overweight and obesity.ResultsThroughout the cohort’s life, the prevalence of overweight increased steadily and stabilized at 45% at 45 y of age. The number of obese 1 and 2 individuals peaked at age 75 y, when 44% of women and 35% of men were obese. The incremental costs per person associated with obesity was highest in older ages and, when accumulated over the lifetime, higher among women (€12,118, €9,495–€15,047) than men (€6,646, €5,252–€10,900). On average, obesity shortened the life expectancy of women/men in the whole cohort by 1.31/1.08 y. The life expectancy for normal-weight women/men at age 30 was 83.31/80.31. The life expectancy was reduced by 1.05/0.65 y if the individual was overweight, obese (2.87/2.71 y), or obese 2 (4.06/4.83 y).ConclusionThe high expected prevalence of obesity in the future will lead to substantial health care costs and large losses in life-years. This underscores the need to implement interventions to reduce the burden of obesity; the MOON model will enable economic evaluations for a wide range of interventions.

Adult Vocational Qualifications Reduce the Social Gradient in Education

Many youth leave school early without an upper secondary education, impeding their chances in the labor market. Early school leavers come disproportionately from families with low parental education. In some countries, there are alternative routes to upper secondary qualifications as adults. Does adult attainment reduce initial social differences in educational attainment, or does it reinforce such differences? Norway is one of the countries where many attain upper secondary qualifications in adulthood. Using individual data from administrative registers, we follow five Norwegian birth cohorts (1973–1977) from age 20 to 40. We document that the association between parental education and upper secondary completion declines monotonically with age, ending at age 40 about 35% below that at age 20. We also document that the alternative routes to adult qualifications recruit students of different family backgrounds. In particular, adults who acquire vocational qualifications via the experience-based route come from families with lower education than other groups. Our evidence suggests that institutions that offer opportunities for certifying qualifications acquired at work mitigate social gradients, fostering more equal opportunities within the education system.

Enterovirus as trigger of coeliac disease: nested case-control study within prospective birth cohort

ObjectiveTo determine whether infection with human enterovirus or adenovirus, both common intestinal viruses, predicts development of coeliac disease.DesignCase-control study nested within Norwegian birth cohort recruited between 2001 and 2007 and...

Early-life exposure to persistent organic pollutants (OCPs, PBDEs, PCBs, PFASs) and attention-deficit/hyperactivity disorder: A multi-pollutant analysis of a Norwegian birth cohort

BackgroundNumerous ubiquitous environmental chemicals are established or suspected neurotoxicants, and infants are exposed to a mixture of these during the critical period of brain maturation. However, evidence for associations with the risk of attention-deficit/hyperactivity disorder (ADHD) is sparse. We investigated early-life chemical exposures in relation to ADHD. MethodsWe used a birth cohort of 2606 Norwegian mother–child pairs enrolled 2002–2009 (HUMIS), and studied a subset of 1199 pairs oversampled for child neurodevelopmental outcomes. Concentrations of 27 persistent organic pollutants (14 polychlorinated biphenyls, 5 organochlorine pesticides, 6 brominated flame retardants, and 2 perfluoroalkyl substances) were measured in breast milk, reflecting the child's early-life exposures. We estimated postnatal exposures in the first 2 years of life using a pharmacokinetic model. Fifty-five children had a clinical diagnosis of ADHD (hyperkinetic disorder) by 2016, at a median age of 13 years. We used elastic net penalized logistic regression models to identify associations while adjusting for co-exposure confounding, and subsequently used multivariable logistic regression models to obtain effect estimates for the selected exposures. ResultsBreast milk concentrations of perfluorooctane sulfonate (PFOS) and β‑hexachlorocyclohexane (β-HCH) were associated with increased odds of ADHD: odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.16, 2.72 and OR = 1.75, 95% CI: 1.22, 2.53, per interquartile range increase in ln-transformed concentrations, respectively. Stronger associations were observed among girls than boys for PFOS (pinteraction = 0.025). p,p′‑Dichlorodiphenyltrichloroethane (p,p′-DDT) levels were associated with lower odds of ADHD (OR = 0.64, 95% CI: 0.42, 0.97). Hexachlorobenzene (HCB) had a non-linear association with ADHD, with increasing risk in the low-level exposure range that switched to a decreasing risk at concentrations above 8 ng/g lipid. Postnatal exposures showed similar results, whereas effect estimates for other chemicals were weaker and imprecise. ConclusionsIn a multi-pollutant analysis of four classes of chemicals, early-life exposure to β-HCH and PFOS was associated with increased risk of ADHD, with suggestion of sex-specific effects for PFOS. The unexpected inverse associations between p,p′-DDT and higher HCB levels and ADHD could be due to live birth bias; alternatively, results may be due to chance findings.

Gut Microbiota in the First 2 Years of Life and the Association with Body Mass Index at Age 12 in a Norwegian Birth Cohort.

Childhood obesity is a growing problem worldwide. Recent research suggests that the gut microbiota may play an important and potentially causal role in the development of obesity and may be one mechanism that explains the transgenerational transmission of obesity risk. Here we examine the early-life gut microbiota at days 4, 10, 30, 120, 365, and 730 and the association with body mass index (BMI) z-scores at age 12 in a Norwegian prospective cohort (n = 165), and evaluate how these BMI-associated taxa relate to maternal overweight/obesity (Ow/Ob) and excessive gestational weight gain (GWG). We performed 16S rRNA gene sequencing on the gut microbiota samples. Taxonomic phylogeny at days 10 and 730 was significantly associated with childhood BMI, and the gut microbiota taxa at two years of age explained over 50% of the variation in childhood BMI in this cohort. The subset of the early-life taxa within the gut microbiota that best predicted later childhood BMI showed substantial overlap with the maternal taxa most strongly associated with maternal Ow/Ob and excessive GWG. Our results show an association between the infant gut microbiota and later BMI, and they offer preliminary evidence that the infant gut microbiota, particularly at 2 years of age, may have potential to help identify children at risk for obesity.IMPORTANCE Understanding the role of the early-life gut microbiota in obesity is important because there may be opportunities for preventive strategies. We examined the relationships between infant gut microbiota at six times during the first two years of life and BMI at age 12 in a birth cohort of 165 children and their mothers. We found that the gut microbiota from early life to two years shows an increasingly strong association with childhood BMI. This study provides preliminary evidence that the gut microbiome at 2 years of age may offer useful information to help to identify youth who are at risk for obesity, which could facilitate more-targeted early prevention efforts.

Flynn effect and its reversal are both environmentally caused

Population intelligence quotients increased throughout the 20th century-a phenomenon known as the Flynn effect-although recent years have seen a slowdown or reversal of this trend in several countries. To distinguish between the large set of proposed explanations, we categorize hypothesized causal factors by whether they accommodate the existence of within-family Flynn effects. Using administrative register data and cognitive ability scores from military conscription data covering three decades of Norwegian birth cohorts (1962-1991), we show that the observed Flynn effect, its turning point, and subsequent decline can all be fully recovered from within-family variation. The analysis controls for all factors shared by siblings and finds no evidence for prominent causal hypotheses of the decline implicating genes and environmental factors that vary between, but not within, families.

Løbende nationale reproduktionsregistre og ad hoc data

ENGLISH SUMMARYOlsen J. National registration in human reproduction and research oriented ad hoc data. Nor JEpidemiol 2017; 27 (1-2): 27-31.The Nordic countries have a long tradition for collecting and storing of data in reproductive health. Theseregisters cover the entire population and focus on health outcomes. They have gradually been made availablefor research and if supplemented with data on potential risk factors in reproductive health, they providea strong basis for research in potential causes of disease in the reproductive system. Several pregnany/birthcohorts have been successful in providing important information in preventive medicine. The most importantof these are the Norwegian birth cohort (MoBa) and the Danish National Birth Cohort (DNBC). Bothinclude about 100,000 newborns. They are based on the rationale that many diseases have causes that startoperating in fetal life – fetal programming of diseases – even diseases that manifest themselves later in life(adult diseases). Examples of historic and more recent findings are presented in the following text.Risk of disclosure of personal data is of concern. We have not had examples of such unwanted disclosureand we want to keep this achievement. We clearly have to do many things different and better in the future.Fortunately, technical solutions are available and promising.The registers and the ad hoc data sources have given the Nordic epidemiologists a leading position inreproductive health. To keep that position, we need to plan new cohorts and train more people. If we do thatwe will be able to continue our collaboration with colleagues all over the world.

Cohort profile: cerebral palsy in the Norwegian and Danish birth cohorts (MOBAND-CP)

PurposeThe purpose of MOthers and BAbies in Norway and Denmark cerebral palsy (MOBAND-CP) was to study CP aetiology in a prospective design.ParticipantsMOBAND-CP is a cohort of more than 210 000...

Adult social position and sick leave: the mediating effect of physical workload.

This study aimed to quantify how much of the adult social gradient in sick leave can be attributed to the mediating role of physical workload while accounting for the role of childhood and adolescent social position and neuroticism. Our sample consisted of 2099 women and 1229 men from a Norwegian birth cohort study (born 1967-1976) who participated in the Nord-Trøndelag Health Study (2006-2008) (HUNT3). Data on sick leave (defined as >16 calendar days; 2006-2009) and social position during childhood, adolescence, and adulthood were obtained from national registers. Study outcome was time-to-first sick leave spell. Physical workload and neuroticism were self-reported in HUNT3. Mediating effects through physical workload were estimated using a method based on the additive hazards survival model. A hypothetical change from highest to lowest group in adult social position was, for women, associated with 51.6 [95% confidence interval (95% CI) 24.7-78.5] additional spells per 100,000 person-days at risk, in a model adjusted for childhood and adolescent social position and neuroticism. The corresponding rate increase for men was 41.1 (95% CI 21.4-60.8). Of these additional spells, the proportion mediated through physical workload was 24% (95% CI 10-49) and 30% (95% CI 10-63) for women and men, respectively. The effect of adult social position on sick leave was partly mediated through physical workload, even while accounting for earlier life course factors. Our findings provide support that interventions aimed at reducing physical workload among those with lower adult social position could reduce sick leave risk.

A novel model to characterize postnatal exposure to lipophilic environmental toxicants and application in the study of hexachlorobenzene and infant growth

BackgroundInfants are exposed to persistent environmental contaminants through breast milk, yet studies assessing the health effects of postnatal exposure are lacking. Existing postnatal exposure assessment is either too simple (lactation exposure model, LEM) or requires complex physiologically-based pharmacokinetic (PBPK) models. ObjectivesWe present equations for postnatal exposure calculations. We applied these equations to study the effect of hexachlorobenzene (HCB) on infant growth in the two first years of life. MethodsHCB was measured in breast milk samples in 449 mother-child pairs participating in the Norwegian birth cohort study HUMIS. We used these concentrations, mother's weight, height and age, together with child's weight at 8 age points, and proportion of milk consumed each month, to calculate HCB concentrations in the infant over age. We then estimated the association between HCB and infant growth using a linear mixed model. ResultsChildren exposed to HCB via mother's milk reached concentrations 1–5 times higher than the mother. HCB was associated with lower weight gain in the first 2years (−33g per unit HCB and month, 95% CI: −38, −27 at 6months). Associations were stronger during the first 3months (−57g per unit HCB and month, 95% CI: −67, −49 at 1month), indicating a critical window of effect. Our equations gave more precise estimates than the LEM. ConclusionOur equations for postnatal exposure of lipophilic environmental toxicants give better results than the LEM and are easier to implement than the complex PBPK models. HCB exposure, especially during the first three months of life, has a negative effect on infant growth up to 2years.